Electrophoresis has become a popular method of analyzing, detecting, and/or purifying biological macromolecules. Separation of macromolecules generally is accomplished through the use of a gelled medium in the form of a tube gel or slab gel. When electrophoresis was introduced, gels were typically made within a laboratory just prior to performing the electrophoretic separation. However, over time, a number of commercial pre-cast gel products have become available. Pre-cast gels offer users operational ease and consistency from experiment to experiment, especially important to laboratories processing large numbers of samples. Because slab gels are generally quite fragile, many pre-cast gel products are packaged within tubs or trays with four sides and a removable top or covering, to support and protect the gel from stresses of shipment and storage. It is particularly convenient for the end-user, and therefore more marketable for the gel manufacturer, if the entire gel tray containing a pre-cast gel is suitable for use “as is”, by simply placing the tray containing the gel into an electrophoresis device.
However, the use of pre-cast gel in a tray within an electrophoresis system presents challenges. Typically, pre-cast gels differ from ordinary “user-prepared” gels in that user-prepared gels often have “open” ends; that is to say, there is nothing between the top and bottom end-edges of the gel and the buffered electrolyte solution used for electrophoresis. Pre-cast gels require support during shipment and storage, and therefore, are bounded on all sides, including the ends, by the four walls of the tray, presenting a barrier between the top and bottom edges of the gel and the buffer solution. Therefore, a system for running multiple pre-cast gels must allow contact between the top surface of the gel and the buffered electrolyte solution at each end of the gel in such a way as to create a substantially uniform flow of current through the gel.
Although a few existing horizontal gel systems permit the simultaneous running of multiple slab gels, for example, the Opossum™ and Hippo™ systems sold by Owl Separation Systems, Inc. (Portsmouth, N.H.), and the Electro-4™ system sold by Thermo Electron Corporation (Waltham, Mass.), the systems were not developed for use with pre-cast gels and adapting them for such use is problematic. Some electrophoresis systems, such as the Opossum, are designed to hold multiple gels in a grid-like fashion within the same plane. Such a design is functional for use with small gels but cannot reasonably be made to fit more than about two large gels due to space and size constraints. Also, the Opossum accommodates user-prepared gels in open-ended casting trays and is not ideally suited, in terms of providing substantially uniform current flow, for the standard four-sided trays used to contain pre-cast gels.
Other systems, such as Hippo and Electro-4, permit vertical stacking of gels, eliminating the problem of counter space, but other issues remain. The stacking supports of these systems are designed to serve as casting trays for preparation of user-prepared gels, wherein the end edges of the prepared gels come into direct contact with the buffered electrolyte solution, and the side edges of the gel meet the sides of the tray portion of the stacking support. Because the stacking supports in these systems are a fixed size, they do not fit all sizes of pre-cast gels. Thus if the pre-cast gel is narrower in width than the tray portion of the stacking support such that the sides of the pre-cast gel do not meet the sidewalls, the gel can tilt to one side when the buffer solution is added to the system, preventing current from running parallel to the length of the gel and distorting the separation pattern. Moreover, existing stacking supports for vertically stackable systems have sidewalls significantly deeper than the depth of most pre-cast gels, creating a significant space above the gel for containing electrolyte buffer solution. Generally, electrophoretic separation is improved when the volume of electrolyte buffer solution across the top surface is kept at a minimum. In the event that extra thick pre-cast slab gels are used, a thickness greater than the fixed distance separating the shelves of the stacking support would make use of existing stacking support systems impossible. Thus, the existing stacking supports are not suitable for use with pre-cast gels of any size and especially when the pre-cast gel is of a different dimension than the stacking support. Further, the existing stacking supports limit the total number of gels in a particular stack to four.
Unfortunately, pre-cast gels cannot be simply stacked without separating supports, because the gels in the stack are in direct contact, obstructing the substantially uniform flow of electrical current through and over each gel and leading to distortion of resultant electrophoretic profiles. Therefore, a need exists for a device that permits the stacking of multiple pre-cast gels within electrophoresis systems and provides appropriate conditions for the substantially uniform flow of electrical current through each of the gels even if the gels within a stack are of different widths.